Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes.
Cell Line, Tumor
Cell Survival
/ genetics
Down-Regulation
/ immunology
Gene Expression Regulation, Neoplastic
/ immunology
Humans
Newcastle disease virus
/ immunology
Oncolytic Virotherapy
/ methods
Oncolytic Viruses
/ immunology
Proto-Oncogene Proteins p21(ras)
/ metabolism
Transforming Growth Factor beta
/ metabolism
Up-Regulation
/ immunology
Urinary Bladder
/ immunology
Urinary Bladder Neoplasms
/ immunology
Wnt Signaling Pathway
/ genetics
beta Catenin
/ metabolism
Bladder Cancer
GSEA
Newcastle disease virus
Persistent infection
Transcriptome analysis
Wnt/β-catenin signalling
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
27 May 2021
27 May 2021
Historique:
received:
22
05
2020
accepted:
12
05
2021
entrez:
28
5
2021
pubmed:
29
5
2021
medline:
21
10
2021
Statut:
epublish
Résumé
Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood. In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR. Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV. This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.
METHODS
METHODS
In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.
RESULTS
RESULTS
Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.
CONCLUSIONS
CONCLUSIONS
This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.
Identifiants
pubmed: 34044804
doi: 10.1186/s12885-021-08345-y
pii: 10.1186/s12885-021-08345-y
pmc: PMC8161962
doi:
Substances chimiques
CTNNB1 protein, human
0
KRAS protein, human
0
Transforming Growth Factor beta
0
beta Catenin
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
625Subventions
Organisme : Kementerian Sains, Teknologi dan Inovasi
ID : FP0514B0021-2 (DSTIN)
Organisme : Ministry of Education, Malaysia
ID : FRGS/2/2014/SKK01/PERDANA/03/1
Organisme : Universiti Putra Malaysia
ID : GT-IPM/2013/9404400
Organisme : Universiti Putra Malaysia
ID : GT-IPS/2013/9397000
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